Abortion is the most common pathological complication of pregnancy. There is evidence for the involvement of prostaglandins in the pathogenesis of premature labor, habitual and threatened abortion, toxemia of pregnancy, spontaneous abortion, and endotoxin-induced abortion. None of the currently available prostaglandin receptor antagonists or inhibitors of prostaglandin synthesis possess the requisite specificity or safety for use as antiabortifacients. Furthermore, inhibitors of prostaglandin synthetase would not be suitable as antiabortifacients since they interfere with the synthesis of prostacyclin which is essential for the patency of the maternal and fetal cardiovascular systems. The purpose of this Grant Proposal is to investigate in detail, in vitro and in vivo in rodents, the reproductive endocrinology, pharmacological selectivity, toxicological profile, and teratogenic potential, of several compounds being developed in our laboratory as potential antiabortifacient agents. These are: (a) 2-propyl-3-keto-dibenzyloxyindanpropionic acid, whose selective PGF2 alpha antagonistic properties have already been reported from our laboratory; (b) the trans- and cis- hydroxy-dibenzyloxyindanpropinic acids, the synthesis of which is being completed in our laboratory; (c) L- and D-hydroxychloroquines and L- and D-chlorochloroquines, whose synthesis has been completed in our laboratory and preliminary pharmacological studies with the D- and L-chlorochloroquines indicate their ability to significantly inhibit the actions of PGF2 alpha in the rat uterus. These prostaglandin receptor antagonists will be tested in rat model systems for premature labor and abortion. Promising compounds will be examined for possible morphological and behavioral teratogenicity to determine their safety for use during pregnancy, and will be used as synthetic leads for the development of additional antiabortifacient agents with prostaglandin antagonistic activity on the uterus.